As the preferred site of entry or colonization for many pathogens, mucosal surfaces of the body play an important role in defence against numerous infections 1. However, induction of mucosal immunity, other than by live oral vaccines, has been problematic. Physiochemical barriers at mucosal surfaces prevent adequate amounts of intact antigen reaching underlying mucosal lymphoid tissue and antigen localization in lymphoid tissues is critical for immune induction 2. The small amount of antigen that does reach these lymphoid sites is largely ignored in a system set up to maintain non-reactivity or tolerance to a heavy burden of food and other benign antigens encountered daily.
Effective delivery of vaccine antigens to Gut Associated Lymphoid Tissue (GALT) has long been recognised as the primary hurdle for mucosal vaccine development. Strategies using the oral route impose a host of obstacles including mucus barriers, degradative gastric acid and alimentary enzymes 3,4. To overcome this, co-delivery of antigen with adjuvants such as cholera toxin has been employed 5, but the clinical application is limited due to the toxicity of such adjuvants. Direct injection of antigen into mucosal lymphoid tissue has also been used 6,7, but such practices would be unlikely to be accepted by vaccinees.
The present inventors postulated that delivering antigens via the blood targeted to mucosal lymphoid tissues may bypass these obstacles. The present inventors tested targeting of antigens to the Mucosal Addressin Cellular Adhesion Molecule-1, (MAdCAM-1), a receptor present in circulatory vessels in the Gut Associated Lymphoid Tissue (GALT) and found that such antigen targeting induced a rapid mucosal IgA response in the gut and augmented (1000 fold) the systemic response to antigen.